In vivo Imaging using Anti-IL-6 Antibodies

Abstract

The present invention is directed to therapeutic methods using IL-6 antagonists such as an Ab 1 antibody or antibody fragment having binding specificity for IL-6 to prevent or treat disease or to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level, reduced serum albumin level, elevated D-dimer or other cogulation cascade related protein(s), cachexia, fever, weakness and/or fatigue prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, and others.

1 - 203 . (canceled) 
     
     
         204 . A method of in vivo imaging which detects the presence of cells which express IL-6 comprising administering an effective amount of at least one anti-IL-6 antibody or antibody fragment, wherein said wherein the antibody or antibody fragment comprises: a variable light chain polypeptide comprising: a polypeptide having at least 90% identity to SEQ ID NO: 709, and a variable heavy chain polypeptide comprising: a polypeptide having at least 90% identity to SEQ ID NO: 657, further wherein said anti-IL-6 antibody or antibody fragment comprises the variable light chain complementarity determining region (CDR) polypeptides of SEQ ID NO:4, 5 and 6 and comprises the variable heavy chain complementarity determining region (CDR) polypeptides of SEQ ID NO:7, 8 or 120, and 9, and wherein said administration further includes the administration of a radionuclide or fluorophore that facilitates detection of the antibody at IL-6 expressing disease sites. 
     
     
         205 . The method of  claim 204 , wherein said in vivo imaging is used to detect IL-6 expressing tumors or metastases in a subject with cancer or metastasis. 
     
     
         206 . The method of  claim 204 , wherein said in vivo imaging is used to detect IL-6 expressing cells at sites of pathology in a subject with a chronic autoimmune disorder associated with IL-6 expressing cells. 
     
     
         207 . The method of  claim 204 , wherein said in vivo imaging is used to detect IL-6 expressing cells at sites of pathology in a subject with a chronic inflammatory disorder associated with IL-6 expressing cells. 
     
     
         208 . The method of  claim 204 , wherein said in vivo imaging is used to facilitate design of an appropriate therapeutic regimen. 
     
     
         209 . The method of  claim 208 , wherein said therapeutic regimen comprises radiotherapy, chemotherapy or a combination thereof. 
     
     
         210 . The method of  claim 204 , wherein the light chain possesses at least 95% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709. 
     
     
         211 . The method of  claim 204 , wherein the heavy chain possesses at least 95% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657. 
     
     
         212 . The method of  claim 204 , wherein the light chain possesses at least 97% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709. 
     
     
         213 . The method of  claim 204 , wherein the heavy chain possesses at least 97% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657. 
     
     
         214 . The method of  claim 204 , wherein the light chain possesses at least 99% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709. 
     
     
         215 . The method of  claim 204 , wherein the heavy chain possesses at least 99% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657. 
     
     
         216 . The method of  claim 204 , wherein the light chain possesses 100% sequence identity to the light chain polypeptide comprised in SEQ ID NO: 709. 
     
     
         217 . The method of  claim 204 , wherein the heavy chain possesses 100% sequence identity to the heavy chain polypeptide comprised in SEQ ID NO: 657. 
     
     
         218 . The method of  claim 204 , wherein said antibody comprises light chain CDR1, CDR2 and CDR3 polypeptides and heavy chain CDR1, CDR2 and CDR3 identical to those on SEQ ID NO:4, 5 and 6 and SEQ ID NO:7, 120 and 9 respectively. 
     
     
         219 . The method of  claim 204 , wherein said antibody comprises light chain CDR1, CDR2 and CDR3 polypeptides and heavy chain CDR1, CDR2 and CDR3 polypeptides identical to those on SEQ ID NO:4, 5 and 6 and SEQ ID NO:7, 8 or 120 and 9 respectively. 
     
     
         220 . The method of  claim 204  wherein the antibody is selected from a human, humanized, single chain, or chimeric antibody and the antibody fragment is selected from a Fab, Fab′, F(ab′) 2 , Fv, or scFv.